Journal
JOURNAL OF COLLOID AND INTERFACE SCIENCE
Volume 355, Issue 2, Pages 374-382Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2010.12.004
Keywords
pH-responsive polymer; Polyphosphazene; Nanoparticles; Drug resistance; Tumor therapy
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Funding
- National Nature Science Foundation of China [30873203, 81072606]
- Science & Technology Department of Zhejiang Province [2009C14008]
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This study involved the construction of self-assembled nanoparticles from novel pH-sensitive amphiphilic polyphosphazenes. These nanoparticles provide fast pH-responsive drug release and have the capability to disturb endosomal membranes. The polymers were prepared by linking N,N-diisopropylethylenediamine (DPA) onto a backbone of PEGylated polyphosphazene. In vitro cell viability measurements demonstrated the superior efficacy of these pH-responsive nanoparticles over free doxorubicin (Dox): the IC50 was over 60 times lower than that of free Dox against a Dox-resistant cell line. Using flow cytometry and confocal microscopy, the further investigation of the intracellular distribution of Dox and fluorescent probes provided evidence that, upon internalization by cells through endocytic pathways, the pH-sensitive polymer would disrupt membranes of endosomal compartments, releasing the cargo drugs into the cytoplasm in a burst-like manner. This resulted in reduced likelihood of drug efflux via exocytosis, and reversal of the drug resistance of the tumor cells. Generally, the pH-responsive nanoparticles designed in this study have achieved their potential as a drug delivery system for tumor therapy applications. (C) 2010 Elsevier Inc. All rights reserved.
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